Medical Department III, University Hospital Aachen, Aachen, Germany.
Hepatology. 2011 Feb;53(2):596-603. doi: 10.1002/hep.24098. Epub 2011 Jan 10.
The recurrence of liver fibrosis after liver transplantation (LT) for hepatitis C virus (HCV) infection is responsible for graft loss and patient mortality. Although the contribution of the immune system to fibrosis recurrence is anticipated, systematic studies evaluating immune parameters as predictive markers of allograft fibrosis are lacking. The infiltration of immune cells into the graft is governed by chemokines. Here we assessed the predictive value of serum levels of chemokines [chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, CXCL11, and chemokine (C-C motif) ligand 2 (CCL2)] with respect to fibrosis recurrence after LT in 90 HCV-infected organ recipients. Chemokines were determined within the first and third years after LT and were correlated with histological fibrosis progression in protocol biopsy samples at 1, 3, 5, and 7 years (median follow-up = 3 years). The association of chemokines with fibrosis progression was assessed by univariate and multivariate analyses and by Cox regression analysis. The results for the analyzed chemokines showed that CXCL10 levels in the first year after LT were strongly associated with early fibrosis recurrence (P = 0.005) independently of risk confounders (including the donor age, HCV viral load, HCV genotype, acute rejection, and inflammatory activity). As assessed by Cox regression analysis, a CXCL10 serum level ≤ 140 pg/mL was significantly predictive of the absence of F2 fibrosis (P = 0.001), whereas a level ≤ 220 pg/mL early after LT predicted the absence of F3 fibrosis during follow-up (P = 0.035).
CXCL10 is an independent biomarker of the recurrence of significant fibrosis after LT for HCV infection. These results might guide patients' care after transplantation and help us to select optimal candidates for antiviral therapy post-LT.
丙型肝炎病毒（HCV）感染患者接受肝移植（LT）后肝纤维化复发是导致移植物丧失和患者死亡的原因。尽管免疫系统对纤维化复发的贡献是可以预期的，但缺乏系统地评估免疫参数作为移植纤维化预测标志物的研究。免疫细胞浸润移植物是由趋化因子控制的。在这里，我们评估了 90 例 HCV 感染器官受者 LT 后血清趋化因子[趋化因子（C-X-C 基序）配体 9（CXCL9）、CXCL10、CXCL11 和趋化因子（C-C 基序）配体 2（CCL2）]水平与纤维化复发的相关性。趋化因子在 LT 后 1 年和 3 年内进行测定，并与 1 年、3 年、5 年和 7 年（中位随访时间为 3 年）的方案活检样本中的组织纤维化进展相关。通过单变量和多变量分析以及 Cox 回归分析评估趋化因子与纤维化进展的相关性。分析趋化因子的结果表明，LT 后第 1 年的 CXCL10 水平与早期纤维化复发强烈相关（P=0.005），独立于风险混杂因素（包括供者年龄、HCV 病毒载量、HCV 基因型、急性排斥反应和炎症活动）。Cox 回归分析表明，LT 后早期 CXCL10 血清水平≤140 pg/mL 显著预测不存在 F2 纤维化（P=0.001），而早期水平≤220 pg/mL 预测随访期间不存在 F3 纤维化（P=0.035）。
CXCL10 是 HCV 感染 LT 后显著纤维化复发的独立生物标志物。这些结果可能指导移植后的患者护理，并帮助我们选择 LT 后抗病毒治疗的最佳候选者。
